Preparation and application of grain worm for treating diabetes

ABSTRACT

This invention discloses the preparation and the application of Grain Worm for treating diabetes or regulating blood insulin level. The Grain Worm can be in the form of dry powder, tincture, or extracts by itself or in a compound. 
     Grain Worm regulates the blood insulin levels and the human blood glucose level for treating diabetes. 
     It has been discovered that Grain Worm can effectively treat diabetes in humans through reducing insulin resistance and improving the β-cell function. The effect of this agent can last a long period of time (2-5 years). This is the first major discovery of using Grain Worm in treating diabetes.

CLAIM OF PRIORITY

The present application is a continuation patent application whichclaims the benefit of, pursuant to 35 U.S.C. Sections 120, 363, and365(c), a currently pending and prior filed international patentapplication, namely, that having Serial No. PCT/CN2019/104316 filed onSep. 4, 2019. The aforementioned international patent application claimspriority to a prior Chinese national patent application, namely, thathaving Serial No. 201910642595.3 filed on Jul. 16, 2019, the contents ofwhich are both incorporated herein, by reference, in their entireties.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention provides a method for preparation of Grain Wormand a method for treating diabetes.

Description of the Related Art

Diabetes is a group of metabolic disorders characterized by high bloodglucose (hyperglycemia) in patients. Hyperglycemia and particularly thetype 2 diabetes mellitus (T2DM) are manifested by both insulinresistance and pancreatic β-cell dysfunction^([1]). The prolongedhyperglycemia causes chronic damage and dysfunction of various tissues,especially on the eyes, kidneys, cardiovascular systems, and nerves. Asdiscovered by modern science, the regulation of human blood glucose is acomplex mechanism involving the secretion and the action of insulin,which is in turn regulated by other signals like glucagon, incretinpeptide, growth factor, neurotransmitters, neuropeptides, and manyothers^([2]). Due to this complexity, it is difficulty to attribute asingle cause for the onset of T2DM. The existing method for treatingT2DM usually starts with lifestyle change followed by the treatment withchemically synthesized medicine. As the T2DM progresses, the patientsmay eventually rely on exogenous insulin to control the blood glucoselevel. The existing method and medicine for treating diabetes are notsatisfactory. Therefore, there are needs for new agents and methods withimproved efficacy to treat diabetes in humans. This invention addressesthese needs.

SUMMARY OF THE INVENTION

The present invention is related to the preparation of a naturallyavailable agent (Grain Worm) and its applications in treating diabetes,through reducing insulin resistance, regulating blood glucose andinsulin levels. The invention provides a method for the preparation ofGrain Worm and its compounds for the application of treating diabetes.Moreover, the invention provides a method for treating diabetes with theGrain Worm and its compounds.

The method encompasses the regulation of blood insulin level with theGrain Worm and its compounds. This invention encompasses the Grain Wormand Grain Worm-based compounds used in any of medicine, dietarysupplement, and food for regulating blood glucose and insulin levels.This invention encompasses the Grain Worm and the Grain Worm-basedcompounds in the form of dry powder, tincture, or extract.

The features of this invention include an agent that is a naturalproduct with minimal toxicity that is easy to use. The agent canregulate blood glucose and insulin levels. The agent and method caneffectively reduce insulin resistance and improve pancreatic β-cellfunction.

Other features and advantages of the present invention will become moreapparent by reading the detailed description of the necessaryembodiments with reference to FIG. 1 and FIG. 2.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a flowchart illustrating the steps to prepare Grain Wormproducts.

FIG. 2 is a flowchart illustrating the steps to use Grain Worm to treatdiabetes.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

The invention is described in detail below with reference to specificembodiments. The examples presented in this document will help those whoare skilled in the field to further understand the present invention,but do not limit the invention in any form. It should be noted that, forthose with basic skill in the field, several variations and improvementscan be made without departing from the concept of this invention. Theseall belong to the protection scope of this invention.

Grain Worm is the name used in “Compendium of Materia Medica” (Anancient bible for traditional Chinese medicine), referring to the Larvaefrom a family of flies, particularly the Chrysomyis Megacephala andLucilia Sericata families. It's commonly called maggot. The larvaecontains protein, lysozyme, amino acids, and others. The Grain Worm isused in the compound in the form of dry powder, tincture, or extract.

Preparation of Grain Worm for Treating Diabetes

The method for preparing the Grain Worm dry powder includes thefollowing steps:

-   -   A1. Wash and scour the collected whole Grain Worm to remove the        dirt on the surface;    -   A2. Soak and disinfect the Grain Worm treated in Step A1, then        rinse and drain;    -   A3. Lyophilize drained Grain Worm into a freeze dryer until it        dries to a water content of less than 10% by weight;    -   A4. The freeze-dried whole larvae are pulverized at low        temperature to obtain the dried Grain Worm powder.        The method for preparing the Grain Worm tincture includes the        following steps:    -   B1. Wash and scour the collected Grain Worm (Larvae) to remove        the dirt on the surface;    -   B2. Soak and disinfect the Grain Worm treated in step B1, then        rinse and drain;    -   B3. Store the drained whole Grain Worm into the liquor and seal        it for a period of time;    -   B4. Take out the sealed Grain Worm and pulverize it at low        temperature to obtain the tincture.

The Grain Worm product can be in the form of capsule, tablet, pill,powder, compound granule, tincture, liquid agent, or a lyophilizedpowder. The Grain Worm extract includes any water-soluble extract,chemical soluble extract from whole Grain Worm or Grain Worm dry powder,and/or their combinations.

Method for Treating Diabetes

The invention also provides a method for treating diabetes based on theaforementioned compound, including the following steps:

Depending on the severity of diabetes (determined by the clinical testdata), a treatment course of 1-6 cycles is recommended. Each cycle isthree months. For each cycle, taking Grain Worm or a compound containingGrain Worm 2-3 times daily. The dosage of Grain Worm is 2 g-30 g perday. The invention also provides a method regulating insulin levelsbased on the aforementioned compound, including the following steps:

Depending on the severity of diabetes (determined by the clinical testdata), a treatment course of 1-6 cycle is recommended. Each cycle isthree months. For each cycle, taking Grain Worm or a compound containingGrain Worm 2-3 times daily. The dosage of Grain Worm is 2 g-30 g perday.

For the patients with pre-diabetes, taking Grain Worm or the compoundcontaining Grain Worm for a period of 1-2 cycles. The dosage of GrainWorm is 2 g-15 g per day.

For the patients with confirmed diabetes, taking Grain Worm or thecompound containing Grain Worm for a period of 4-6 cycles. The dosage ofGrain Worm is 3 g-30 g per day for the first and second cycles; thedosage of Grain Worm is 3 g-15 g per day for the second cycle to sixthcycle.

Compared to the existing technology, the Grain Worm is a natural productwith minimal toxicity. The active ingredient for treating diabetes isthe whole Grain Worm. Modern medical research proves that the Grain Wormcontains protein, fat, chitosan, antibacterial peptides and variousamino acids. The lyophilized Grain Worm powder of this inventionincludes all the active ingredients of the whole Grain Worm, and theGrain Worm extract is mainly composed of fatty acids and/or proteins,peptides, amino acids, and the like. It was discovered that Grain Wormcan regulate blood glucose and insulin levels. In the verification ofthe effect, it was found that the patients who were treated with GrainWorm could significantly reduce insulin resistance and improve β-cellfunctions. The Grain Worm does not have the drug resistance, thetoxicity, and side effects of hypoglycemia, nephrotoxicity and hepatictoxicity.

Based on the results of Oral Glucose Tolerance Test (OGTT) before andafter treatment with Grain Worm, the patients have their insulinresistance reduced and β-cell function improved, thus the blood glucoseis controlled. The long-term effect after discontinuation of allmedications has been observed. This is the first major discovery ofusing traditional Chinese medicine in treating diabetes.

This invention converts Grain Worm into a medicine, is convenient tocarry and take, and has a high clinical effectiveness (up to 90% for acertain group of patients, based on existing statistics). The patientsare followed up to five years after the treatment.

Grain Worm formulated compound, on the other hand, is an all-naturalproduct that can effectively treat diabetes. It can regulate human bloodglucose level bi-directionally, by improving the balance in biochemicalprocesses.

EXAMPLES

The method for preparing the Grain Worm dry powder includes thefollowing steps:

-   -   A1. Wash and scour the collected whole Grain Worm to remove the        dirt on the surface;    -   A2. Soak and disinfect the Grain Worm treated in Step A1, then        rinse and drain;    -   A3. Put the drained Grain Worm into a freeze dryer (−20° C. to        −50° C., equivalent to −4° F. to −58° F.) until it dries to a        water content of less than 10% by weight (the yield is about        25%); It takes about 24 hours.    -   A4. The freeze-dried whole larvae are pulverized at low        temperature to obtain the dried Grain Worm powder.

The method for preparing the Grain Worm tincture includes the followingsteps:

-   -   B1. Wash and scour the collected Grain Worm (Larvae) to remove        the dirt on the surface;    -   B2. Soak and disinfect the Grain Worm treated in step B1, then        rinse and drain;    -   B3. Store the drained whole Grain Worm into the liquor and seal        it for at least 2 months;    -   B4. Take out the sealed Grain Worm and pulverize at low        temperature to obtain the tincture.

In Steps A2 and B2, the disinfection solution used for the immersiondisinfection is a mixture of water and peroxyacetic acid disinfectionstock solution, and the soaking time is 10 minutes; The volume ratio ofthe water to peroxyacetic acid disinfection stock solution is 1:400.

In Step B3, the weight ratio of the whole Grain Worm to liquor is 1:4 to2:3; The liquor is a pure grain liquor with an alcohol content of 55% to70%.

The Grain Worm product can be in the form of capsule, tablet, pill,powder, compound granule, tincture, liquid agent, or a lyophilizedpowder.

The Grain Worm extract includes any water-soluble extract, chemicalsoluble extract from whole Grain Worm or Grain Worm dry powder, and/ortheir combinations.

For the patients with pre-diabetes, the recommended initial dosage is 1g-1.5 g of Grain Worm powder before meal, 2-3 times a day, for a periodof 1-2 cycles.

For the patients with mild diabetes, the recommended initial dosage is1.5 g of Grain Worm powder before each meal, 3 times a day, plus 1 g-10g of Grain Worm tincture before bedtime, for the first cycle. Startingon the second cycle, the dosage is 1.5 g of Grain Worm powder beforeeach meal, 3 times a day only. A total of 4 cycles of treatment isrecommended.

For the patients with moderate diabetes, the recommended initial dosageis 1.5 g of Grain Worm powder before each meal, 3 times a day, plus 1g-10 g of Grain Worm tincture before bedtime, for the first cycle.Starting on the second cycle, take 1.5 g of Grain Worm powder beforeeach meal, 3 times a day only. A total of 5 cycles of treatment isrecommended.

For the patients with severe diabetes, the combined uses of Grain Wormdry powder, Grain Worm tincture, and the prescribed (western) medicine(only at the beginning of the first cycle for most cases) for 5-6 cyclesare recommended.

Recommended dosage: For the 1^(st) cycle, take 1.5 g Grain Worm beforeeach meal, three times a day. 1 g-10 g of Grain Worm tincture twice aday; one after breakfast and the other before bedtime. Combined with theregular (prescribed) western medicine(s). No exogenous insulin is neededduring the treatment course. Monitor the glucose level daily. Theregular prescribed (western) medicine(s) may be totally discontinuedafter blood glucose level is controlled. From the 2^(nd) to 6^(th)cycle, take 1.5 g of Grain Worm dry powder before each meal, 3 times aday. Based on patient's response to the treatment, 1 g-10 g of GrainWorm tincture may be taken before bedtime every day.

Examples of Medical Efficacy

The following are several T2DM patients treated using Grain Wormproduct. The diagnostic standards are from most recent World HealthOrganization (WHO) publications. Note that the blood glucose unit ismmol/L in this document. To convert the unit in mg/dL (commonly used inthe US), multiply the value in mmol/L by 18.

The first example is for Patient J, a 34 year-old female. Prior to theGrain Worm treatment, the patient's OGTT data (Table 1) showed that shehad hypoglycemia when fasting and hyperglycemia postprandially after 75g glucose intake. The peak of blood glucose level was at two-hour timepoint. Because the patient was breast-feeding at that moment, thepatient had not done the lifestyle change or any medication for glucosecontrol. The treatment for Patient J is as follows: the patient tookcapsules containing 1.5 g of Grain Worm dry powder before meal, threetimes (i.e., 3×1.5 g) a day.

After 116 days of treatment, the Patient J took a second OGTT test(Table 1). The fasting blood glucose level changed from hypoglycemia(3.41 mmol/L or 61.38 mg/dl) to normal (4.88 mmol/L or 87.84 mg/dl). Thetwo-hour blood glucose level decreased from 9.65 mmol/L (or 173.7 mg/dl)to 6.49 mmol/L (or 116.82 mg/dl). And the peak blood glucose level movedfrom 2-hour to 1-hour time point. The ratio of the area under the curve(AUC) for insulin to the AUC for glucose increased by 130%, indicatingthe improvement of β-cell function. Assessed using the WHO criteria, thepatient has completely returned to normal.

TABLE 1 Comparison of OGTT results before and after treatment forPatient J 30- 1- 2- 3- Fasting Minute hour hour hour Before PlasmaGlucose 3.41  6.62 8.84 9.65  7.14 (mmol/L) Plasma Insulin 0.7 11.2 15.315.0 12.2 (mIU/L) After Plasma Glucose 4.88 N/A 9.14 6.49 N/A (mmol/L)Plasma Insulin 3.2 N/A 30.8 32.1 N/A (mIU/L)

The second example is for Patient Z, a 55 year-old male. The patient hada history of diabetes for 5 years before treatment. The OGTT data priorto Grain Worm treatment showed that the patient had fasting glucoselevel exceeded 7.0 mmol/L and 2-hour glucose level exceeded 11.1 mmol/L(Table 2). The treatment for Patient Z is as follows: Grain Wormcapsules 3 times a day, a total of 4.5 g of Grain Worm dry powder daily,plus 15 ml of Grain Worm tincture before bedtime per day. The patient'sblood glucose level was closely monitored every day. At the 19^(th) dayof the treatment, the patient stopped all western medicine.

Patient Z took another OGTT test (see Table 2) after 6 months of GrainWorm treatment (2 treatment cycles). Results showed that patient'sfasting glucose level decreased from 8.41 to 5.41 mmol/L and 2-hourglucose level decreased from 17.92 to 10.71 mmol/L. Using HOMA-1^([3])model, the patient's insulin resistance reduced by 73%. And the ratio ofthe AUC of insulin to the AUC of glucose increased by 5.3%, indicatingthe improvement of β-cell function.

TABLE 2 Comparison of OGTT results before and after treatment forPatient Z 30- 1- 2- 3- Fasting Minute hour hour hour Before PlasmaGlucose 8.41 N/A 16.72 17.92 11.87 (mmol/L) Plasma Insulin 10.85 N/A80.16 38.21 21.13 (mIU/L) After Plasma Glucose 5.41 10.66 11.97 10.716.41 (mmol/L) Plasma Insulin 4.62 29.27 34.11 45.54 16.53 (mIU/L)

The third example is for Patient C, a 54 year-old female. Before theGrain Worm treatment, the patient had had a history of diabetes for 16years and relied on insulin injection (24 units per day) for controllingblood glucose level for about 14 years. The treatment for Patient C isas follows: Grain Worm capsules 3 times a day, a total of 4.5 g of GrainWorm dry powder daily, plus 10 ml of Grain Worm tincture before bedtimeper day. There are no insulin injections for Patient C, who stopped allwestern medicine after Day 28 of the treatment.

After 2 treatment cycles (180 days), Patient C took another OGTT (Table3). The insulin resistance^([3]) decreased by 46%. The ratio of the AUCof insulin to the AUC of glucose increased by 3.5%, indicating theimprovement of β-cell function. Most importantly, the patient has nolonger relied on insulin injection to achieve the blood glucose control.

TABLE 3 Comparison of OGTT results before and after treatment forPatient C 30- 1- 2- 3- OGTT Fasting minute hour hour hour Before Glucose7.5 N/A 19.1 18.8 10.2 (with (mmol/L) Insulin Insulin 8.67 N/A 26.4327.39 16.23 injection) (mIU/L) After Glucose 6.35 11.72 14 14.48 7.64(without (mmol/L) insulin Insulin 5.58 14.3  19.09 24.51 11.3 injection)(mIU/L)

The fourth example is for Patient Y, a 58 year-old male. Prior to theGrain Worm treatment, the patient's blood glucose levels at both fastingand 2-hour were extremely high (Table 4). The treatment for Patient Y isas follows: Grain Worm capsules 3 times a day, a total of 4.5 g of GrainWorm dry powder daily, plus 15 ml of Grain Worm tincture before bedtimeper day. Patient Y stopped all western medicine after Day 31 of thetreatment.

At the 42^(nd) day of treatment, i.e., 11 days after stopped all westernmedicine, Patient Y took another OGTT test (Table 4). The glucosetolerance was improved significantly. The insulin resistance^([3])decreased by 34%. The ratio of the AUC of insulin to the AUC of glucoseincreased by 1,330%. The 30-minute insulinogenic index^([4]) increasedby 2,888%. The oral disposition index^([5]) increased by 4,317%. Allthese indexes indicate the patient's β-cell function has beendramatically improved.

TABLE 4 Comparison of OGTT results before and after treatment forPatient Y 30- 1- 2- 3- Fasting Minute hour hour hour Before PlasmaGlucose 3.41  6.62 8.84 9.65  7.14 (mmol/L) Plasma Insulin 0.7 11.2 15.315.0 12.2 (mIU/L) After Plasma Glucose 4.88 N/A 9.14 6.49 N/A (mmol/L)Plasma Insulin 3.2 N/A 30.8 32.1 N/A (mIU/L)

What is claimed is:
 1. A method of regulating blood insulin levels in anindividual in need thereof, the method comprising administering to theindividual an effective amount of a composition comprising Grain Wormfora treatment course of at least one cycle wherein each cycle has aduration of at least three months.
 2. The method of claim 1 wherein saideffective amount of said composition comprising Grain Worm treatsdiabetes.
 3. The method of claim 1 wherein said composition comprisingGrain Worm is ingested by the individual.
 4. The method of claim 1wherein said composition comprising Grain Worm comprises a dietarysupplement.
 5. The method of claim 1 wherein said composition comprisingGrain Worm comprises dry powder Grain Worm.
 6. The method of claim 1wherein said composition comprising Grain Worm comprises a Grain Wormtincture.
 7. The method of claim 1 wherein said composition comprisingGrain Worm comprises a Grain Worm extract.
 8. The method of claim 1wherein said composition comprising Grain Worm comprises a lyophilizedpowder.
 9. The method of claim 1 wherein said composition comprisinggrain worm is structured to be injected.
 10. The method of claim 1,wherein the composition comprising Grain Worm is administered at leastonce per day.
 11. The method of claim 10 wherein said compositioncomprising said Grain Worm comprises between approximately 2 g to 30 gof said Grain Worm.
 12. The method of claim 11 wherein said compositioncomprising said Grain Worm is administered [between] two [to three]times per day.
 13. The method of claim 1, wherein the method treatspre-diabetes, said pre-diabetes treatment course comprising 1-2 cycles,wherein each cycle has a duration of approximately three months andcomprises administering said composition for a total dosage of 2 g to 15g of said Grain Worm per day during each of said cycles.
 14. The methodof claim 2, wherein said diabetes treatment is a treatment coursecomprising at least 4-6 cycles, wherein at least a first two of saidcycles comprise administering said composition for a total dosage of 3 gto 30 g of said Grain Worm per day, and wherein the remaining ones ofsaid cycles comprise administering said composition for a total dosageof 3 g to 15 g of said Grain Worm per day.
 15. The method of clam 14wherein each of said cycles has a duration of approximately threemonths.
 16. The method of claim 1, wherein the treatment coursecomprises at least 4 cycles, wherein each cycle has a duration ofapproximately three months and wherein said composition comprising GrainWorm is administered at least once per day during each of said cycles.17. The method of claim 1, wherein the treatment course comprises nomore than 6 cycles, wherein each cycle has a duration of approximatelythree months and wherein said composition comprising Grain Worm isadministered at least once per day during each of said cycles.
 18. Themethod of claim 11 wherein said composition comprising said Grain Wormis administered three times per day.
 19. The method of claim 1, whereinthe method treats pre-diabetes, said pre-diabetes treatment coursecomprising at least 1 cycle, wherein each cycle has a duration ofapproximately three months and comprises administering said compositionfor a total dosage of 2 g to 15 g of said Grain Worm per day during saidcycle.
 20. The method of claim 14, wherein said diabetes treatmentcourse comprises 6 cycles, at least a first two of said cyclescomprising administering said composition for a total dosage of 3 g to30 g of said Grain Worm per day, and the remaining ones of said cyclescomprising administering said composition for a total dosage of 3 g to15 g of said Grain Worm per day.